Procedures for determining the presence or absence of specific organisms or viruses in a test sample commonly rely upon nucleic acid-based probe testing. To increase the sensitivity of these tests, an amplification step is often included to increase the number of potential nucleic acid target sequences present in the test sample. There are many procedures for amplifying nucleic acids which are well known in the art, including, but not limited to, the polymerase chain reaction (PCR), (see, e.g., Mullis, “Process for Amplifying, Detecting, and/or Cloning Nucleic Acid Sequences,” U.S. Pat. No. 4,683,195), transcription-mediated amplification (TMA), (see, e.g., Kacian et al., “Nucleic Acid Sequence Amplification Methods,” U.S. Pat. No. 5,399,491), ligase chain reaction (LCR), (see, e.g., Birkenmeyer, “Amplification of Target Nucleic Acids Using Gap Filling Ligase Chain Reaction,” U.S. Pat. No. 5,427,930), and strand displacement amplification (SDA), (see, e.g., Walker, “Strand Displacement Amplification,” U.S. Pat. No. 5,455,166). A review of several amplification procedures currently in use, including PCR and TMA, is provided in HELEN H. LEE ET AL., NUCLEIC ACID AMPLIFICATION TECHNOLOGIES (1997).
Amplification, however, raises concerns about cross-contamination, since transferring even a minute amount of target-containing sample to a target-negative sample could lead to the production of billions of target sequences in the “negative” sample, possibly resulting in a false-positive that might otherwise have been negative in the absence of an amplification step. The source of a contaminating sample transfer may be an aerosol or bubbles released from the sample tube of a sample collection kit when a cap component of the sample tube is removed by a practitioner. To minimize such sources of contamination, it would be desirable to have a sample carrier capable of substantially immobilizing sample tubes having penetrable caps which are designed and constructed to limit the release of an aerosol or bubbles when penetrated by a standard positive displacement pipette tip. Penetrable caps designed and constructed to limit the release of potentially contaminating material are disclosed by Anderson et al., “Collection Device and Method for Removing a Fluid Substance from the Same,” U.S. Patent Application Publication No. US 2001-0041336 A1, and Kacian et al., “Penetrable Cap,” U.S. Application Publication No. US 2002-0127147 A1.
By securely immobilizing sample tubes in a sample carrier, the sample tubes can be centered in an automated sampling system so that sample tubes can be sequentially penetrated by distinct pipette tips and air from within the sample tubes can be vented and filtered as the pipette tips enter the sample tubes. Moreover, if properly centered, the aerosol and bubble barriers of these penetrable caps can also function to remove sample residue from the outside of these pipette tips as they are being withdrawn from the sample tubes.
To secure sample tubes outfitted with penetrable caps in a sample carrier, the sample carrier must exert sufficient force against the sample tubes to prevent them from being extracted from the sample carrier during sampling, especially in automated sampling procedures where manual restraint of the sample tubes is not possible. The force exerted against the sample tubes, known as the “retaining force,” may be supplied by leaf springs, for example, which are oriented so that the springs are biased against the sample tubes as they are inserted into the sample carrier. Sample carriers incorporating leaf springs are disclosed by, for example, Dale et al., “Sample Carrier and Drip Shield for Use Therewith,” U.S. Patent Application Publication No. US 2003-0017084 A1. The force required to retain any given sample tube in a sample carrier during sampling will largely depend upon the withdrawal force. The “withdrawal force” is the upward force required to fully remove a fluid transfer device (e.g., pipette tip) from the sample tube after the cap component has been penetrated. As the withdrawal force increases, the retaining force must likewise increase. And the greater the retaining force, the more force practitioners must exert to insert sample tubes into conventional sample carriers, making the sample carriers more difficult to control and exposing practitioners to possible repetitive motion injuries, such as carpal tunnel syndrome.
Thus, a need exists for a sample carrier which provides an adequate retaining force for maintaining sample tubes in the sample carrier during sampling, while at the same time minimizing the force required to insert sample tubes into the sample carrier. Ideally, the sample carrier would be configured for use with an automated sampling device and would include means for centering the cap component under the sampling device. Secondary or failsafe means for retaining sample tubes in the sample carrier would also be desirable.